Background: Progression free survival (PFS) and overall survival (OS) appear to differ across trials, even when pts receive the same regimen (REG). This analysis aimed to benchmark the clinical outcomes in the 2^nd line treatment of metastatic colorectal cancer (mCRC). Methods: Individual patient (pt) data was available on 6,462 pts with mCRC enrolled in 7 2^ndline clinical trials (8 REGs) in the ARCAD database. Regimens used in at least two trials included FOLFIRI +/- an EGFR inhibitor (EGFRi), FOLFOX +/- a VEGF inhibitor (VEGFi), and irinotecan (IRI). Descriptive statistics were used to describe pt demographics. Multivariable Cox models were used to assess differences (DIFFs) in PFS and OS, while p-value <0.05 were considered statistically significant (SS). Results: 500-1400 pts received each REG (see Table). Median OS and PFS differed by 0.2 to 4.6 months (mo) and 0.8 to 2.5 mo across trials within the same REG. These DIFFs were SS except for PFS in REGs containing FOLFIRI +/- EGFRi. After multivariable adjustment, all DIFFs in OS were attenuated and non-significant. DIFFs in PFS attenuated for most REGs but remained SS for FOLFOX and IRI. Conclusions: After multivariable adjustment, there were no SS DIFFs in outcomes across trials within the same REG, with the exception of PFS in FOLFOX and IRI. The initial observed DIFFs in outcomes could be due to confounding factors and the remaining SS DIFFs in PFS in FOLFOX and IRI may be due to variation in definition of progression across trials. Therefore, caution is warranted when using historical data to design future trials.

* in months # adjusted for age, gender, ECOG PS, prior treatment, liver metastasis, number of metastatic sites